The release of oxytocin and prostaglandins appears to be the final step in the initiation of parturition. These two endogenous substances are powerful oxytocic agents. We have shown that oxytocin and possibly also other uterotonic therapeutic drugs stimulate prostaglandin biosynthesis and release in the uterus. We postulate that the marked increase in sensitivity of the parturient uterus to oxytocin may be related to the enhanced prostaglandin biosynthesis and the oxytocin-induced prostaglandin release in the term uterus. One of the objectives of this project is to test the validity of this hypothesis. We will study the relationship between oxytocin sensitivity and uterine prostaglandin levels in rats during the last four days of pregnancy. We will also determine the effects of inhibition of prostaglandin biosynthesis on the development of oxytocin sensitivity in pregnant rats. A second objective of this project is to delineate the uterotonic action and the prostaglandin-releasing action of oxytocin and the receptors involved. We will also seek to elucidate the biochemical mechanism of the prostaglandin-releasing action of oxytocin. Specific oxytocin antagonists (oxytocin analogs with antioxytocin activity) and isotopic techniques will be utilized in these pharmacological and biochemical studies. A third objective is directed to the development of a safe and effective method for the control of premature labor. We have a number of oxytocin antagonists that have been found effective in inhibiting oxytocin-induced uterine contractions in pregnant rats. We will investigate the efficacy of these oxytocin anatogonists in the human myometrial strips, with the specific aim to develop useful agents for the control of premature labor.